Testosterone Replacement Therapy & Anemia

[Michael Scally MD]

Zhang LT, Shin YS, Kim JY, Park JK. Could Testosterone Replacement Therapy in Hypogonadal Men Ameliorate Anemia, a Cardiovascular Risk Factor? An Observational, 54-week Cumulative Registry Study. J Urol. https://www.sciencedirect.com/science/article/pii/S0022534715051502

PURPOSE: This study was to investigate if testosterone undecanoate in patients with hypogonadism attenuates anemia and the risk for cardiovascular disease.

MATERIALS AND METHODS: A registry study consisted of 58 participants with subnormal total testosterone level (<2.35 ng/ml) and at least mild symptoms of testosterone deficiency.

All the patients were injected with 1,000 mg of testosterone undecanoate on initial visit, followed by injection at 6, 18, 30, 42 and 54 weeks. Serum hormones, Hb, Hct, anemia risk factors, lipid profiles, whole blood viscosity and anthropometry were measured.

RESULTS: Total testosterone (from 1.87 +/- 1.09 to 5.52 +/- 1.92 ng/ml, p <0.001) and free testosterone (from 3.04 +/- 2.03 to 7.23 +/- 2.90 pg/ml, p <0.001) were restored by testosterone undecanoate therapy. Hb and Hct significantly increased after testosterone undecanoate therapy by an average of 2.46 g/dl (p <0.001) and 3.03% (p <0.001), respectively.

Prevalence of anemia (from 29.6 to 10.0%) significantly decreased (p <0.001) and patients with anemia showed a significant increase in erythropoietin (p = 0.047) after testosterone undecanoate therapy.

Reduction in total cholesterol (from 165.89 +/- 39.16 to 153.80 +/- 154.27 mg/dl, p = 0.002), higher whole blood viscosity and increased Hct were observed until 54 weeks compared with baseline, however whole blood viscosity and Hct stabilized after 18 weeks.

CONCLUSIONS: 54-week testosterone undecanoate decreased the prevalence of anemia and components of metabolic syndrome. A longer duration testosterone undecanoate therapy of more than 18 weeks may be effective and safe in reducing the blood viscosity and improving anemia.

 

[Michael Scally MD]

Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia

Context: Testosterone treatment of hypogonadal men improves their hemoglobin, but the mechanism is not understood.

Objective: To investigate possible mechanisms by which testosterone stimulates erythropoiesis in hypogonadal older men with unexplained or iron-deficiency anemia.

Design: The Anemia Trial of The Testosterone Trials, a placebo-controlled study in older, hypogonadal men.

Setting: Twelve academic medical centers.

Participants: 95 hypogonadal men (testosterone <275 ng/mL) ≥65 years with anemia (hemoglobin <12.7 g/dL). They were classified as having unexplained (58) or iron deficiency anemia (37).

Intervention: Testosterone or placebo gel for one year.

Main outcome measures: Markers of iron metabolism during the first three months of treatment.

Results: Testosterone replacement significantly (p<0.001) increased hemoglobin in the 58 men who had unexplained anemia (adjusted mean difference 0.58 g/dL; 95% CI 0.31-0.85). Testosterone replacement tended to increase hemoglobin in the 37 men who had iron deficiency (0.38 g/dL; -0.19,0.95), but the response was more variable and not statistically significant (p=0.19).

In men with unexplained anemia, testosterone replacement suppressed hepcidin [-8.2 ng/mL (-13.7, -2.7) p=0.004] and ferritin [-19.6 µg/L (-32.8, -6.3) p =0.004], but in men with iron deficiency, testosterone replacement did not.

The decrease in hepcidin was moderately correlated with the increase in hemoglobin in the men with unexplained anemia (correlation coefficient -0.35, p = 0.01) but not in those with iron deficiency anemia (correlation coefficient -0.07, p = 0.73 ).

Conclusions: Testosterone replacement of older hypogonadal men with unexplained anemia stimulates erythropoiesis associated with increased iron mobilization. This effect appears to be attenuated by iron deficiency.

Artz AS, Stephens-Shields AJ, Bhasin S, Ellenberg SS, Cohen HJ, Snyder PJ. Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia [published online ahead of print, 2020 Aug 12]. J Clin Endocrinol Metab. 2020;dgaa521. doi:10.1210/clinem/dgaa521 https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgaa521/5891785?redirectedFrom=fulltext